In both veterinary medicine and human medicine, the ability to initiate and regulate hematopoiesis is of great importance. A variety of diseases and immune disorders, as well as malignancies, appear to be related to disruptions within the hematopoietic system. Many of these disorders could be alleviated and/or cured by repopulating the hematopoietic system with progenitor cells which, when triggered to differentiate, would overcome the individual's deficiency. In humans, a current replacement therapy is bone marrow transplantation. This form of therapy, however, is both painful for both donor and recipient, and is of severe danger to the recipient, particularly when the grafts are allogeneic. Even though prior to bone marrow transplantation, the donor and recipient are matched with respect to HLA types, approximately half of the allogeneic bone marrow transplant recipients develop Graft Versus Host Disease (GVHD). Current therapy for GVHD is imperfect, and the disease can be disfiguring and/or lethal. Thus, risk of GVHD restricts the use of bone marrow transplantation to patients with otherwise fatal diseases, such as severe immunodeficiency disorders, severe aplastic anemia, and malignancies.
The potential benefits of bone marrow transplantation have stimulated research on the cause and prevention of GVHD. In animal studies it has been shown that GVHD is caused by donor T lymphocytes. Removal of T lymphocytes from donor marrow inocula ("grafts") attenuated the subsequent development of GVHD in mice, dogs and monkeys. Trials in humans, in which bone marrow has been depleted of T lymphocytes by a variety of methods, however, has not prevented or cured GVHD in bone marrow recipients.
A potential alternative form of therapy for hematopoietic disorders is treatment of the individual with any one or combination of colony stimulating factors. The process of blood cell formation, by which a small number of self-renewing stem cells give rise to lineage committed progenitor cells that subsequently proliferate and differentiate to produce the circulating mature blood cells, is sustained throughout life by a group of glycoprotein hormonal growth factors. These hormones are known collectively as the colony stimulating factors (CSFs).